7N3I

Crystal structure of the SARS-CoV-2 receptor binding domain in complex with the human neutralizing antibody Fab fragment C098

7N3I の概要

• エントリーDOI: 10.2210/pdb7n3i/pdb
• 分子名称: Spike protein S1, C098 Fab heavy chain, C098 Fab light chain, ... (5 entities in total)
• 機能のキーワード: severe acute respiratory syndrome coronavirus-2, spike protein, neutralizing antibodies, immune system, immune system-viral protein complex, immune system/viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2, COVID-19 virus); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 71996.18

構造登録者

Flyak, A.I.,Bjorkman, P.J.,Barnes, C.O. (登録日: 2021-06-01, 公開日: 2021-08-04, 最終更新日: 2024-10-09)

主引用文献

Muecksch, F.,Weisblum, Y.,Barnes, C.O.,Schmidt, F.,Schaefer-Babajew, D.,Wang, Z.,C Lorenzi, J.C.,Flyak, A.I.,DeLaitsch, A.T.,Huey-Tubman, K.E.,Hou, S.,Schiffer, C.A.,Gaebler, C.,Da Silva, J.,Poston, D.,Finkin, S.,Cho, A.,Cipolla, M.,Oliveira, T.Y.,Millard, K.G.,Ramos, V.,Gazumyan, A.,Rutkowska, M.,Caskey, M.,Nussenzweig, M.C.,Bjorkman, P.J.,Hatziioannou, T.,Bieniasz, P.D.
Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations.
Immunity, 54:1853-, 2021

PubMed Abstract: Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Spike receptor-binding domain (RBD)-specific antibodies from 5 individuals shortly after infection and later in convalescence to determine the impact of maturation over months. In addition to increased affinity and neutralization potency, antibody evolution changed the mutational pathways for the acquisition of viral resistance and restricted neutralization escape options. For some antibodies, maturation imposed a requirement for multiple substitutions to enable escape. For certain antibodies, affinity maturation enabled the neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. Antibody-antigen structures revealed that these properties resulted from substitutions that allowed additional variability at the interface with the RBD. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses.

PubMed: 34331873
DOI: 10.1016/j.immuni.2021.07.008

実験手法

X-RAY DIFFRACTION (2.03 Å)